Ferroelectric, Dielectric and Electromechanical Performance of Ba0.92Ca0.08Ti0.95Zr0.05O3 Ceramics with an Enhanced Curie Temperature.

Ba0.92Ca0.08Ti0.95Zr0.05O3 (BCZT8-5) ceramic materials have been scarcely studied as lead-free piezo/ferroelectrics despite their enhanced Curie temperature (>100 °C) with respect to most studied BCZT compositions. In this work, homogeneous dense BCZT8-5 ceramics with grain size in the range of 20 µm, and optimum ferroelectric, dielectric, and electromechanical performance, were prepared by the mixed oxides route using moderate synthesis (1250 °C-2 h) and sintering (1400 °C-2 h) conditions. Thickness-poled thin disks and monomodal shear plate resonators were used for the determination of piezoelectric coefficients, coupling factors, elastic, and dielectric permittivity coefficients, including all losses, by iterative analysis of impedance curves at resonance. Furthermore, the thermal evolution of the piezoelectric characteristics at resonance was determined to assess the enhanced working range of the ceramics (≈100 °C). Ferroelectric hysteresis loops and strains vs. electric-field butterfly loops were also measured and showed soft behavior with Ec = 2 kV/cm, Pr = 12 µC/cm2 after a maximum applied field of 3 kV was used. The ceramics showed a high endurance of P-E cycles to electrical fatigue up to 107 cycles. Moreover, dielectric properties as a function of temperature were also accomplished and showed nearly normal ferroelectric behavior, characteristic of samples with low crystallographic disorder. Overall, these ceramics showed high sensitivity and higher stability than other currently studied BCZT compositions.

Executive summary of the position paper on the use of enteral nutrition in advanced dementia.

Dementia is an increasingly prevalent disease in our environment, with significant health and social repercussions. Despite the available scientific evidence, there is still controversy regarding the use of enteral tube nutrition in people with advanced dementia. This document aims to reflect on the key aspects of advanced dementia, tube nutritional therapy and related ethical considerations, as well as to respond to several frequent questions that arise in our daily clinical practice.

Diabetes remission after malabsorptive bariatric surgery.

Obesity and diabetes are two closely related disorders. Lifestyle changes and drug treatment do not achieve successful diabetes remission. A treatment option for these patients is bariatric surgery (BS). The partial and complete remission rates vary, depending on the type of technique used (restrictive or malabsorptive), with malabsorptive surgery being more effective in terms of both weight reduction and diabetes remission (DR). Different scales (DiaRem, Ad-DiaRem or 5y-Ad-DiaRem) predict the probability of DR after BS, particularly after gastric bypass surgery. Some studies report higher DR rates in surgery with a greater malabsorptive component. Our aim was to study the benefits of BS at one year and 5 years in terms of the weight and blood glucose profile in patients with obesity and type 2 diabetes mellitus; assess percentage DR according to ADA criteria; determine the DR predictive capacity of different scores; and examine which variables predict DR at one and five years after biliopancreatic diversion (BPD). Percentage overweight reduction and the decrease in both blood glucose and HbA1c were greater with BPD. Complete diabetes remission was approximately 80% at one and 5 years after BS. In general, the scores that determine the probability of DR show poor discriminative capacity in malabsorptive surgery. Presurgery HbA1c predicts DR at one and 5 years after BPD. The type of surgery performed should be individualized, based on the severity of diabetes and the specific characteristics of each patient.

Diabetes remission after malabsorptive bariatric surgery. / Remisión de diabetes tras cirugía bariátrica malabsortiva.

Obesity and diabetes are two closely related disorders. Lifestyle changes and drug treatment do not achieve successful diabetes remission. A treatment option for these patients is bariatric surgery (BS). The partial and complete remission rates vary, depending on the type of technique used (restrictive or malabsorptive), with malabsorptive surgery being more effective in terms of both weight reduction and diabetes remission (DR). Different scales (DiaRem, Ad-DiaRem or 5y-Ad-DiaRem) predict the probability of DR after BS, particularly after gastric bypass surgery. Some studies report higher DR rates in surgery with a greater malabsorptive component. Our aim was to study the benefits of BS at one year and 5 years in terms of the weight and blood glucose profile in patients with obesity and type 2 diabetes mellitus; assess percentage DR according to ADA criteria; determine the DR predictive capacity of different scores; and examine which variables predict DR at one and five years after biliopancreatic diversion (BPD). Percentage overweight reduction and the decrease in both blood glucose and HbA1c were greater with BPD. Complete diabetes remission was approximately 80% at one and 5 years after BS. In general, the scores that determine the probability of DR show poor discriminative capacity in malabsorptive surgery. Presurgery HbA1c predicts DR at one and 5 years after BPD. The type of surgery performed should be individualized, based on the severity of diabetes and the specific characteristics of each patient.

Postoperative enteral immunonutrition in head and neck cancer patients: Impact on clinical outcomes.

BACKGROUND: Head and neck cancer patients have a high rate of complications during the postoperative period that could increase their morbidity rate. Arginine has been shown to improve healing and to modulate inflammation and immune response. The aim of our study was to assess whether use of arginine-enriched enteral formulas could decrease fistulas and length of stay (LoS). METHODS: A retrospective study was conducted in patients who had undergone head and neck cancer surgery and were receiving enteral nutrition through a nasogastric tube in the postoperative period between January 2012 and May 2018. The differences associated to use of immunoformula vs. standard formulas were analysed. Sociodemographic, anthropometric, and nutritional intervention variables, as well as nutritional parameters, were recorded during the early postoperative period. Occurrence of complications (fistulas), length of hospital stay, readmissions, and 90-day mortality were recorded. RESULTS: In a univariate analysis, patients who received nutritional support with immunonutrition had a lower fistula occurrence rate (17.91% vs. 32.84%; p=0.047) and a shorter mean LoS [28.25 (SD 16.11) vs. 35.50 (SD 25.73) days; p=0.030]. After adjusting for age, energy intake, aggressiveness of surgery and tumour stage, fistula occurrence rate and LoS were similar in both groups irrespective of the type of formula. CONCLUSIONS: Use of arginine-enriched enteral nutrition appears to decrease the occurrence of fistulas in the postoperative period in patients with head and neck cancer, with a resultant reduction in length of hospital stay. However, the differences disappeared after adjusting for age, tumour stage, or aggressiveness of the surgery.

Influence of thyroid peroxidase antibodies on TSH levels of pregnant women and maternal-fetal complications. / Influencia de los anticuerpos antiperoxidasa tiroidea en los valores de TSH de gestantes y en las complicaciones materno-fetales.

INTRODUCTION: During pregnancy, thyroid peroxidase (TPO) antibodies may increase the risk of developing subclinical hypothyroidism (SCH). Both conditions appear to be associated to maternal-fetal complications. The objectives of this study were to analyze if a relationship exists between TSH and TPO levels during pregnancy and the potential effects on gestational and perinatal complications, and to assess whether detectable, but not positive, TPO levels have an impact on development of gestational SCH. METHODS: A prospective study was conducted at the Leon Health Area (CAULE), where universal screening for gestational thyroid dysfunction is performed between weeks 7-13 of pregnancy. Data on TSH and TPO levels and gestational and perinatal complications were collected for all 2016 deliveries. Positive TPO antibodies were defined as values≥35IU/mL. In a previous study, a TSH level>3.72mU/L was established as the cut-off value for gestational SCH. RESULTS: Records corresponding to 1,980 deliveries at CAULE, 21 abortions, and 18 deliveries outside the hospital were analyzed. Of the 1,670 pregnant women screened (84.34%), 142 (8.50%) had positive TPO antibodies and their presence was associated to diagnosis of SCH (P<0.01) and to significantly higher mean TSH levels (3.51mU/L vs. 2.46mU/L, P=0.03). There were no significant differences in gestational or neonatal complications. In the group with undetectable TPO antibodies (<10lU/mL), the mean TSH levels was slightly lower than in the group with TPO values ranging from 10-35 IU/mL, but the difference was not significant (P=0.89). CONCLUSION: Presence of positive TPO antibodies is associated to higher TSH levels and higher risk of gestational SCH, but does not increase the rate of maternal-fetal complications.

Efficacy of enteral nutritional support after hospital discharge in major gastrointestinal surgery patients: a systematic review

INTRODUCTION: Nutritional support for malnourished patients undergoing gastrointestinal surgery reduces the complication rate and shortens the length of stay. The efficacy of nutritional support after hospital discharge was analyzed in this systematic review. METHODS: The search strategy (nutrition OR "enteral nutrition" OR "nutritional supplements" OR "oral nutritional supplements" OR "sip feed" OR "sip feeding" OR "dietary counseling") AND ("patient discharge" OR discharge OR postdischarge) AND (surgery OR operation OR "surgical procedure") was followed in Medline, CENTRAL, and Trip databases. Inclusion criteria comprised: type of study (randomized controlled trial), language (English, Spanish), and subjects (patients undergoing gastrointestinal surgery). The risk of bias was assessed by using the Cochrane methodology. RESULTS: Five studies which were published in six different articles and recruited 446 patients were included. A high risk of bias was detected for most of them. Nutritional support improved energy intake and protein intake when high-protein oral supplements were provided. The intervention was associated with better weight prognosis, but the data about body composition were inconsistent. In most of the trials, nutritional intervention did not enhance functional capacity or quality of life. None of the studies analyzed the effects on complications after discharge. CONCLUSION: Nutritional support provided at discharge may increase dietary intake and improve body weight, but the low quality of studies can weaken the validity of results.

Appetite disorders in cancer patients: Impact on nutritional status and quality of life.

Cancer patients are at high risk of malnutrition due to several symptoms such as lack of appetite. The aim of this study was to determine the prevalence of different appetite disorders in cancer patients and their influence on dietary intake, nutritional status, and quality of life. We conducted a cross-sectional study of cancer patients at risk of malnutrition. Nutritional status was studied using Subjective Global Assessment, anthropometry, and grip strength. Dietary intake was evaluated with a 24-h recall, and patients were questioned about the presence of changes in appetite (none, anorexia, early satiety, or both). Quality of life was measured using EORTC-QLQ-C30. Multivariate analysis was performed using linear regression. 128 patients were evaluated. 61.7% experienced changes in appetite: 31% anorexia, 13.3% early satiety, and 17.2% both. Appetite disorders were more common in women and with the presence of cachexia. The combination of anorexia and satiety resulted in a lower weight and BMI. However, there were no significant effects on energy or macronutrient intake among different appetite alterations. Patients with a combination of anorexia and early satiety had worse overall health perception, role function, and fatigue. Appetite disorders are highly prevalent among cancer patients at risk of malnutrition. They have a significant impact on nutritional status and quality of life, especially when anorexia and early satiety are combined.

Coexistence of Factor VII Deficiency and Hereditary Spastic Paraplegia in Two Siblings.

We present the case of two patients aged 12 years and 7 years who were referred to our hospital for factor VII deficiency inherited in an autosomal recessive pattern, who had suffered from previous multiple joint haemarthroses. They presented with fine motor symptoms and difficulty in walking. During physical examination we observed neurological symptoms (general hypotonia, muscular hypotrophy, exaggerated tendon reflexes, pes cavus, and spastic gait). Given that the symptoms were not justified by the deficiency of coagulation factor VII and on suspicion of hereditary spastic paraplegia (HSP), tests were carried out. Findings from the tests confirmed the diagnosis of HSP (axonal degeneration of the central motor pathway and pyramidal tracts), further complicated by mixed neuropathy. This disease was also inherited in an autosomal recessive pattern with no direct genetic association with factor VII deficiency. Neurological symptoms had gone unnoticed due to a history of multiple joint haemarthrosis; musculoskeletal examination led to a satisfactory differential diagnosis. Haematological prophylaxis was commenced with rFVIIa at 30 mcg/kg, three days per week. A rehabilitation programme was prescribed so that the patient could remain independent for as long as possible, based on orthosis, physiotherapy, and occupational therapy. Response to treatment is currently satisfactory and no new bleeding has presented. As far as we are aware, the coexistence of these two diseases (factor VII deficiency and HSP) has not been previously reported in the literature.

Optimization of a recombinant human growth hormone purification process using quality by design.

This work describes a strategy to optimize a downstream processing of a recombinant human growth hormone (rhGH) by incorporating a quality by design approach toward meeting higher quality specifications. The optimized process minimized the presence of impurities and degradation by-products during manufacturing by the establishment of in-process controls. Capillary zone electrophoresis, reverse phase, and size-exclusion chromatographies were used as analytical techniques to establish new critical process parameters for the solubilization, capture, and intermediate purification steps aiming to maintain rhGH quality by complying with pharmacopeial specifications. The results indicated that the implemented improvements in the process allowed the optimization of the specific recovery and purification of rhGH without compromising its quality. In addition, this optimization facilitated the stringent removal of the remaining impurities in further polishing stages, as demonstrated by the analysis of the obtained active pharmaceutical ingredient.

CHRONIC ENTERITIS IN PATIENTS UNDERGOING PELVIC RADIOTHERAPY: PREVALENCE, RISK FACTORS AND ASSOCIATED COMPLICATIONS.

INTRODUCTION: the radiation of tumours located in pelvic organs can cause mucositis in the bowel. The aim of this study was to determine the prevalence, risk factors, and complications of chronic radiation enteritis in patients who had received pelvic radiotherapy. PATIENTS AND METHODS: cross-sectional study recruiting 150 patients that had been treated with radiation therapy during the year 2008 because of a prostate, cervical, endometrial or rectal cancer. The patients were asked about symptoms related to enteritis, and about changes in body weight and in dietary patterns. Sex, age, treatment modalities, acute enteritis, and type of cancer were considered possible risk factors, and were analysed with univariate and multivariate methods. RESULTS: the study included 100 patients, 84% males, median age 72.3 years. Chronic radiation enteritis was found in 20% of the patients, most of them grade 1 (45%). Furthermore, 10% had lost ≥ 5 kg of weight, 3% had been hospitalized due to diarrhoea or bowel obstruction, and 11% had changed their diet, mainly by removing vegetables, legumes and pastry. Male gender, age, previous acute radiation enteritis, and chemotherapy were associated with chronic enteritis, but only chemotherapy remained independently related to bowel toxicity after multivariate analysis (OR = 3.59 [95% CI 1.20-10.73]). CONCLUSION: chronic enteritis is common among patients treated with pelvic radiotherapy, especially if chemotherapy is associated. The complication rate is low, but a significant number of patients change their usual diet in order to prevent symptoms.

Introducción: la radiacion de los tumores de la cavidad pelvica puede provocar mucositis a nivel intestinal. El objetivo de nuestro estudio fue determinar la prevalencia, los factores de riesgo y las complicaciones de la enteritis radica cronica en los pacientes tratados con radioterapia pelvica. Pacientes y métodos: estudio transversal sobre 150 pacientes tratados con radioterapia pelvica durante el ano 2008 debido a un cancer de prostata, cervix, endometrio o recto. Se interrogo a los pacientes sobre la presencia de sintomas sugestivos de enteritis y sobre cambios en el peso habitual y modificaciones en su dieta. Los parametros considerados como posibles factores de riesgo de enteritis cronica (sexo, edad, tratamiento antitumoral, enteritis aguda previa y tipo de tumor) se analizaron con metodos univariantes y multivariantes. Resultados: el estudio incluyo finalmente a 100 pacientes, el 84% varones, con una mediana de edad de 72,3 anos. Se encontro una prevalencia de enteritis radica cronica del 20%, en la mayoria de grado 1 (45%). Por otra parte, el 10% referian una perdida de peso ≥ 5 kg, el 3% habian requerido hospitalizacion debido a diarrea incoercible o a obstruccion intestinal, y el 11% habian modificado su patron de alimentacion habitual, reduciendo principalmente el consumo de verduras, legumbres y dulces. Se encontro asociacion entre la enteritis radica cronica y el sexo masculino, la edad, la enteritis radica aguda previa y la quimioterapia, pero solo esta resulto asociarse de forma independiente con el desarrollo de enteritis radica cronica despues del analisis multivariante (OR = 3,59 [95% CI 1,20­10,73]). Conclusión: la enteritis cronica es una entidad frecuente en los pacientes tratados con radioterapia pelvica, sobre todo cuando se asocia con quimioterapia. La tasa de complicaciones por esta patologia es baja, pero un numero importante de pacientes realiza modificaciones en su dieta habitual para aliviar o evitar la sintomatologia derivada de aquella.

Kinetics and conformational stability studies of recombinant leucine aminopeptidase.

Leucine aminopeptidase from Vibrio proteolyticus is a broad specificity N-terminal aminopeptidase that is widely used in pharmaceutical processes where the removal of N-terminal residues in recombinant proteins is required. We previously reported the expression of a heterologous construction of the mature protein fused to a 6-histidine tag that presents a reasonable refolding rate for its use at industrial level. Here, we investigate this recombinant leucine aminopeptidase (rLAP) to explain the gain of activity observed when incubated at 37 °C after its production. Unfolding transitions of rLAP as a function of urea concentration were monitored by circular dichroism (CD) and fluorescence (FL) spectroscopy exhibiting single transitions by both techniques. Free energy change for unfolding measured by CD and FL spectroscopy are 2.8 ± 0.4 and 3.7 ± 0.4 kcal mol(-1), respectively. Thermal stability conformation of rLAP is 2.6 ± 0.1 and 6.1 kcal mol(-1) for CD and Nano-Differential Scanning Calorimetry (Nano-DSC), respectively. Enzyme activity was assessed with L-leucine-p-nitroanilide (L-pNA) as substrate. The catalytic efficiency was 3.87 ± 0.10 min(-1) µM(-1) at 37 °C and pH 8.0. Kinetic and conformation studies show differences between the enzyme native and rLAP; however rLAP is selective and specific to remove N-terminal groups from amino acids.